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Canadian Journal of Microbiology Oct 2021Dengue is a vector-borne viral disease caused by the flavivirus dengue virus (DENV). Approximately 400 million cases and 22 000 deaths occur due to dengue worldwide... (Review)
Review
Dengue is a vector-borne viral disease caused by the flavivirus dengue virus (DENV). Approximately 400 million cases and 22 000 deaths occur due to dengue worldwide each year. It has been reported in more than 100 countries in tropical and subtropical regions. A positive-stranded enveloped RNA virus (DENV) is principally transmitted by mosquitoes. It has four antigenically distinct serotypes, DENV-1 to DENV-4, with different genotypes and three structural proteins and seven non-structural proteins. Clinical symptoms of dengue range from mild fever to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), with thrombocytopenia, leucopenia, and increased vascular permeability. Although primary infection causes activation of immune responses against DENV serotypes, the severity of the disease is enhanced via heterotypic infection by various serotypes as well as antibody-dependent enhancement (ADE). The first licensed DENV vaccine was tetravalent CYD Denvaxia, but it has not been approved in all countries. The lack of a suitable animal model, a proper mechanistic study in pathogenesis, and ADE are the main hindrances in vaccine development. This review summarizes the current knowledge on DENV epidemiology, biology, and disease aetiology in the context of prevention and protection from dengue virus disease.
Topics: Animals; Antibodies, Viral; Biology; Dengue; Dengue Virus; Mosquito Vectors
PubMed: 34171205
DOI: 10.1139/cjm-2020-0572 -
Viruses Jul 2020Dengue, caused by infection of any of four dengue virus serotypes (DENV-1 to DENV-4), is a mosquito-borne disease of major public health concern associated with... (Review)
Review
Dengue, caused by infection of any of four dengue virus serotypes (DENV-1 to DENV-4), is a mosquito-borne disease of major public health concern associated with significant morbidity, mortality, and economic cost, particularly in developing countries. Dengue incidence has increased 30-fold in the last 50 years and over 50% of the world's population, in more than 100 countries, live in areas at risk of DENV infection. We reviews DENV biology, epidemiology, transmission dynamics including circulating serotypes and genotypes, the immune response, the pathogenesis of the disease as well as updated diagnostic methods, treatments, vector control and vaccine developments.
Topics: Aedes; Animals; Dengue; Dengue Vaccines; Dengue Virus; Genome, Viral; Genotype; Humans; Mosquito Control; Mosquito Vectors; Virus Replication
PubMed: 32751561
DOI: 10.3390/v12080829 -
Viruses Sep 2021Dengue is a mosquito-borne viral disease (arboviral) caused by the Dengue virus. It is one of the prominent public health problems in tropical and subtropical regions... (Review)
Review
Dengue is a mosquito-borne viral disease (arboviral) caused by the Dengue virus. It is one of the prominent public health problems in tropical and subtropical regions with no effective vaccines. Every year around 400 million people get infected by the Dengue virus, with a mortality rate of about 20% among the patients with severe dengue. The Dengue virus belongs to the Flaviviridae family, and it is an enveloped virus with positive-sense single-stranded RNA as the genetic material. Studies of the infection cycle of this virus revealed potential host targets important for the virus replication cycle. Here in this review article, we will be discussing different stages of the Dengue virus infection cycle inside mammalian host cells and how host proteins are exploited by the virus in the course of infection as well as how the host counteracts the virus by eliciting different antiviral responses.
Topics: Antibodies, Viral; Dengue; Dengue Virus; Host Microbial Interactions; Humans; Life Cycle Stages; RNA, Viral; Virus Replication
PubMed: 34696397
DOI: 10.3390/v13101967 -
Viruses Nov 2022Dengue virus (DENV) infection is one of the major public health concerns around the globe, especially in the tropical regions of the world that contribute to 75% percent... (Review)
Review
Dengue virus (DENV) infection is one of the major public health concerns around the globe, especially in the tropical regions of the world that contribute to 75% percent of dengue cases. While the majority of DENV infections are mild or asymptomatic, approximately 5% of the cases develop a severe form of the disease that is mainly attributed to sequential infection with different DENV serotypes. The severity of dengue depends on many immunopathogenic mechanisms involving both viral and host factors. Emerging evidence implicates an impaired immune response as contributing to disease progression and severity by restricting viral clearance and inducing severe inflammation, subsequently leading to dengue hemorrhagic fever and dengue shock syndrome. Moreover, the ability of DENV to infect a wide variety of immune cells, including monocytes, macrophages, dendritic cells, mast cells, and T and B cells, further dysregulates the antiviral functions of these cells, resulting in viral dissemination. Although several risk factors associated with disease progression have been proposed, gaps persist in the understanding of the disease pathogenesis and further investigations are warranted. In this review, we discuss known mechanisms of DENV-mediated immunopathogenesis and its association with disease progression and severity.
Topics: Humans; Dengue Virus; Dengue; Serogroup; Macrophages; Disease Progression
PubMed: 36423184
DOI: 10.3390/v14112575 -
Reviews in Medical Virology Jan 2022Infection with dengue virus (DENV) leads to symptoms variable from dengue fever to severe dengue, which has posed a huge socioeconomic and disease burden to the world... (Review)
Review
Infection with dengue virus (DENV) leads to symptoms variable from dengue fever to severe dengue, which has posed a huge socioeconomic and disease burden to the world population, particularly in tropical and subtropical regions. To date, four serotypes of DENV (DENV-1 to DENV-4) have been identified to sustain the transmission cycle in humans. In the past decades, dengue incidences have become more frequent, and four serotypes and various genotypes have been identified in PR China. Several large-scale dengue outbreaks and frequent local endemics occurred in the southern and coastal provinces, and the imported dengue cases accounted primarily for the initiation of the epidemics. No antiviral drug exists for dengue, and no vaccine has been approved to use in PR China, however strategies including public awareness, national reporting system of infectious diseases and public health emergencies, vector mosquito control, personal protection, and improved environmental sanitation have greatly reduced dengue prevalence. Some new technologies in vector mosquito control are emerging and being applied for dengue control. China's territory spans tropical, subtropical, and temperate climates, hence understanding the dengue status in China will be of beneficial for the global prevention and control of dengue. Here, we review the dengue status in PR China for the past decades and the strategies emerging for dengue control.
Topics: Aedes; Animals; China; Dengue; Dengue Virus; Humans; Mosquito Vectors; Severe Dengue
PubMed: 34235802
DOI: 10.1002/rmv.2245 -
Journal of Microbiology, Immunology,... Dec 2020Dengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to...
BACKGROUND
Dengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). We conducted a literature review to analyze the risks of DHF and current perspectives for DHF prevention and control.
METHODS
According to the PRISMA guidelines, the references were selected from PubMed, Web of Science and Google Scholar database using search strings containing a combination of terms that included dengue hemorrhagic fever, pathogenesis, prevention and control. Quality of references were evaluated by independent reviewers.
RESULTS
DHF was first reported in the Philippines in 1953 and further transmitted to the countries in the region of South-East Asia and Western Pacific. Plasma leakages is the main pathophysiological hallmark that distinguishes DHF from DF. Severe plasma leakage can result in hypovolemic shock. Various factors are thought to impact disease presentation and severity. Virus virulence, preexisting dengue antibodies, immune dysregulation, lipid change and host genetic susceptibility are factors reported to be correlated with the development of DHF. However, the exact reasons and mechanisms that triggers DHF remains controversial. Currently, no specific drugs and licensed vaccines are available to treat dengue disease in any of its clinical presentations.
CONCLUSION
This study concludes that antibody-dependent enhancement, cytokine dysregulation and variation of lipid profiles are correlated with DHF occurrence. Prompt diagnosis, appropriate treatment, active and continuous surveillance of cases and vectors are the essential determinants for dengue prevention and control.
Topics: Animals; Antibodies, Viral; Culicidae; Dengue Virus; Female; Humans; Male; Mosquito Vectors; Severe Dengue; Virulence
PubMed: 32265181
DOI: 10.1016/j.jmii.2020.03.007 -
Nature Oct 2021Dengue virus causes approximately 96 million symptomatic infections annually, manifesting as dengue fever or occasionally as severe dengue. There are no...
Dengue virus causes approximately 96 million symptomatic infections annually, manifesting as dengue fever or occasionally as severe dengue. There are no antiviral agents available to prevent or treat dengue. Here, we describe a highly potent dengue virus inhibitor (JNJ-A07) that exerts nanomolar to picomolar activity against a panel of 21 clinical isolates that represent the natural genetic diversity of known genotypes and serotypes. The molecule has a high barrier to resistance and prevents the formation of the viral replication complex by blocking the interaction between two viral proteins (NS3 and NS4B), thus revealing a previously undescribed mechanism of antiviral action. JNJ-A07 has a favourable pharmacokinetic profile that results in outstanding efficacy against dengue virus infection in mouse infection models. Delaying start of treatment until peak viraemia results in a rapid and significant reduction in viral load. An analogue is currently in further development.
Topics: Animals; Antiviral Agents; Dengue; Dengue Virus; Disease Models, Animal; Female; Male; Membrane Proteins; Mice; RNA Helicases; Serine Endopeptidases; Viral Load; Viral Nonstructural Proteins; Viremia; Virus Replication
PubMed: 34616043
DOI: 10.1038/s41586-021-03990-6 -
MBio Oct 2023Dengue virus (DENV) is a major human pathogen that can cause hemorrhagic fever and shock syndrome. One important factor of DENV pathogenicity is non-structural protein 1...
Dengue virus (DENV) is a major human pathogen that can cause hemorrhagic fever and shock syndrome. One important factor of DENV pathogenicity is non-structural protein 1 (NS1), a glycoprotein that is secreted from infected cells. Here we study the mode of action of the widely used drug ivermectin, used to treat parasitic infections and recently shown to lower NS1 blood levels in DENV-infected patients. We found that ivermectin blocks the nuclear transport of transcription factors required for the expression of chaperones that support the folding and secretion of glycoproteins, including NS1. Impairing nuclear transport of these transcription factors by ivermectin or depleting them from infected cells dampens NS1 folding and thus its secretion. These results reveal a novel mode of action of ivermectin that might apply to other flaviviruses as well.
Topics: Humans; Dengue Virus; Dengue; Endoplasmic Reticulum Chaperone BiP; Ivermectin; Karyopherins; Molecular Chaperones; Transcription Factors; Viral Nonstructural Proteins
PubMed: 37702492
DOI: 10.1128/mbio.01441-23 -
Archives of Virology Jun 2023Dengue is a disease caused by a flavivirus that is transmitted principally by the bite of an Aedes aegypti mosquito and represents a major public-health problem. Many... (Review)
Review
Dengue is a disease caused by a flavivirus that is transmitted principally by the bite of an Aedes aegypti mosquito and represents a major public-health problem. Many studies have been carried out to identify soluble factors that are involved in the pathogenesis of this infection. Cytokines, soluble factors, and oxidative stress have been reported to be involved in the development of severe disease. Angiotensin II (Ang II) is a hormone with the ability to induce the production of cytokines and soluble factors related to the inflammatory processes and coagulation disorders observed in dengue. However, a direct involvement of Ang II in this disease has not been demonstrated. This review primarily summarizes the pathophysiology of dengue, the role of Ang II in various diseases, and reports that are highly suggestive of the involvement of this hormone in dengue.
Topics: Animals; Humans; Dengue Virus; Dengue; Angiotensin II; Flavivirus; Aedes; Cytokines
PubMed: 37368044
DOI: 10.1007/s00705-023-05814-6 -
Frontiers in Cellular and Infection... 2020Dengue is an acute febrile disease triggered by dengue virus. Dengue is the widespread and rapidly transmitted mosquito-borne viral disease of humans. Diverse symptoms... (Review)
Review
Dengue is an acute febrile disease triggered by dengue virus. Dengue is the widespread and rapidly transmitted mosquito-borne viral disease of humans. Diverse symptoms and diseases due to Dengue virus (DENV) infection ranges from dengue fever, dengue hemorrhagic fever (life-threatening) and dengue shock syndrome characterized by shock, endothelial dysfunction and vascular leakage. Several studies have linked the severity of dengue with the induction of inflammasome. DENV activates the NLRP3-specific inflammasome in DENV infected human patients, mice; specifically, mouse bone marrow derived macrophages (BMDMs), dendritic cells, endothelial cells, human peripheral blood mononuclear cells (PBMCs), keratinocytes, monocyte-differentiated macrophages (THP-1), and platelets. Dengue virus mediated inflammasome initiates the maturation of IL-1β and IL-18, which are critical for dengue pathology and inflammatory response. Several studies have reported the molecular mechanism through which (host and viral factors) dengue induces inflammasome, unravels the possible mechanisms of DENV pathogenesis and sets up the stage for the advancement of DENV therapeutics. In this perspective article, we discuss the potential implications and our understanding of inflammasome mechanisms of dengue virus and highlight research areas that have potential to inhibit the pathogenesis of viral diseases, specifically for dengue.
Topics: Animals; Dengue; Dengue Virus; Endothelial Cells; Humans; Inflammasomes; Leukocytes, Mononuclear; Mice; Severity of Illness Index
PubMed: 33014899
DOI: 10.3389/fcimb.2020.00489